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In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7–10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14–21 days, median 14 days). [ABSTRACT FROM AUTHOR]

The utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal surveillance swabs has not been well-described in children. This retrospective, cohort study yielded a negative predictive value of 99.4% for an initial negative MRSA nasal surveillance swab in 165 hospitalized children with a suspected infection and clinical cultures obtained from a likely site of infection. [ABSTRACT FROM AUTHOR]

Background Antibiotic-associated adverse events (AEs) in hospitalized children have not been comprehensively characterized. Methods We conducted a retrospective observational study of children hospitalized at The Johns Hopkins Hospital receiving ≥24 hours of systemic antibiotics. Consensus regarding antibiotic-associated AE definitions was established by 5 infectious diseases specialists prior to data collection. Two physicians reviewed potential AEs and determined whether they were more likely than not related to antibiotics after comprehensive manual chart review. Inpatient and post-discharge AEs were identified using the Epic Care Everywhere network. AEs evaluated from the initiation of antibiotics until 30 days after antibiotic completion included gastrointestinal, hematologic, hepatobiliary, renal, neurologic, dermatologic, cardiac, myositis, vascular access device-related events, and systemic reactions. Ninety-day AEs included Clostridioides difficile infections, multidrug-resistant organism infections, and clinically significant candidal infections. The impact of AEs was categorized as necessitating additional diagnostic testing, changes in medications, unplanned medical encounters, prolonged or new hospitalizations, or death. Results Among 400 antibiotic courses, 21% were complicated by at least one AE and 30% occurred post-discharge. Each additional day of antibiotics was associated with a 7% increased odds of an AE. Of courses complicated by an AE, 66% required further intervention. Hematologic, gastrointestinal, and renal AEs were the most common, accounting for 31%, 15%, and 11% of AEs, respectively. AEs complicated 35%, 35%, 19%, and 18% of courses of piperacillin-tazobactam, tobramycin, ceftazidime, and vancomycin, respectively. Conclusions More than 1 in 5 courses of antibiotics administered to hospitalized children are complicated by AEs. Clinicians should weigh the risk of harm against expected benefit when prescribing antibiotics. [ABSTRACT FROM AUTHOR]

Background National guidelines recommend 10 days of antibiotics for children with community-acquired pneumonia (CAP), acknowledging that the outcomes of children hospitalized with CAP who receive shorter durations of therapy have not been evaluated. Methods We conducted a comparative effectiveness study of children aged ≥6 months hospitalized at The Johns Hopkins Hospital who received short-course (5–7 days) vs prolonged-course (8–14 days) antibiotic therapy for uncomplicated CAP between 2012 and 2018 using an inverse probability of treatment weighted propensity score analysis. Inclusion was limited to children with clinical and radiographic criteria consistent with CAP, as adjudicated by 2 infectious diseases physicians. Children with tracheostomies; healthcare-associated, hospital-acquired, or ventilator-associated pneumonia; loculated or moderate to large pleural effusion or pulmonary abscess; intensive care unit stay >48 hours; cystic fibrosis/bronchiectasis; severe immunosuppression; or unusual pathogens were excluded. The primary outcome was treatment failure, a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death (all determined to be likely attributable to bacterial pneumonia) within 30 days after completing antibiotic therapy. Results Four hundred and thirty-nine patients met eligibility criteria; 168 (38%) patients received short-course therapy (median, 6 days) and 271 (62%) received prolonged-course therapy (median, 10 days). Four percent of children experienced treatment failure, with no differences observed between patients who received short-course vs prolonged-course antibiotic therapy (odds ratio, 0.48; 95% confidence interval,.18–1.30). Conclusions A short course of antibiotic therapy (approximately 5 days) does not increase the odds of 30-day treatment failure compared with longer courses for hospitalized children with uncomplicated CAP. [ABSTRACT FROM AUTHOR]

With the current carbapenem-resistant organism crisis, conventional approaches to optimizing pharmacokinetic-pharmacodynamic parameters are frequently inadequate, and traditional salvage agents (eg, colistin, tigecycline, etc) confer high toxicity and/or have low efficacy. However, several β-lactam agents with activity against carbapenem-resistant organisms were approved recently by the US Food and Drug Administration, and more are anticipated to be approved in the near future. The primary goal of this review is to assist infectious disease practitioners with preferentially selecting 1 agent over another when treating patients infected with a carbapenem-resistant organism. However, resistance to some of these antibiotics has already developed. Antibiotic stewardship programs can ensure that they are reserved for situations in which other options are lacking and are paramount for the survival of these agents. [ABSTRACT FROM AUTHOR]

In a multicenter retrospective study, we sought to determine the optimal vancomycin trough concentration that would impact the duration of methicillin-resistant Staphylococcus aureus bacteremia in children. We found that a median vancomycin trough concentration of <10 µg/mL within the first 72 hours may be associated with a longer duration of bacteremia compared to a median trough concentration of ≥10 µg/mL. [ABSTRACT FROM AUTHOR]

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure in adults. The epidemiology, clinical outcomes, and risk factors for treatment failure associated with MRSA bacteremia in children are poorly understood. METHODS: Multicenter, retrospective cohort study of children <18 years hospitalized with MRSA bacteremia across 3 tertiary care children's hospitals from 2007 to 2014. Treatment failure was defined as persistent bacteremia >3 days, recurrence of bacteremia within 30 days, or attributable 30-day mortality. Potential risk factors for treatment failure, including the site of infection, vancomycin trough concentration, critical illness, and need for source control, were collected via manual chart review and evaluated using multivariable logistic regression. RESULTS: Of 232 episodes of MRSA bacteremia, 72 (31%) experienced treatment failure and 23% developed complications, whereas 5 (2%) died within 30 days. Multivariable analysis of 174 children treated with vancomycin with steady-state vancomycin concentrations obtained found that catheter-related infections (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13-0.94) and endovascular infections (OR, 4.35; 95% CI: 1.07-17.7) were associated with lower and higher odds of treatment failure, respectively, whereas a first vancomycin serum trough concentration <10 µg/mL was not associated with treatment failure (OR, 1.34; 95% CI, 0.49-3.66). Each additional day of bacteremia was associated with a 50% (95% CI: 26%-79%) increased odds of bacteremia-related complications. CONCLUSIONS: Hospitalized children with MRSA bacteremia frequently suffered treatment failure and complications, but mortality was low. The odds of bacteremia-related complications increased with each additional day of bacteremia, emphasizing the importance of achieving rapid sterilization. [ABSTRACT FROM AUTHOR]

The role of cefepime for extended-spectrum β-lactamase (ESBL) bacteremia is unclear if susceptible in vitro. In a propensity score-matched study of patients with ESBL bacteremia, risk of death was 2.87 times higher for patients receiving cefepime compared with carbapenems (95% confidence interval [CI], .88-9.41). We compared 14-day mortality of patients with ESBL bacteremia receiving empiric cefepime versus empiric carbapenem therapy in a propensity score-matched cohort. There was a trend towards increased mortality in the cefepime group (hazard ratio, 2.87; 95% CI, .88-9.41), which enhances the existing literature suggesting that cefepime may be suboptimal for invasive ESBL infections. [ABSTRACT FROM AUTHOR]

Background. The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. Methods. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 μg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. Results. A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). Conclusions. PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents. [ABSTRACT FROM AUTHOR]

Background Children with osteomyelitis transitioned to oral step-down therapy experience similar outcomes to those treated with outpatient parenteral antibiotic therapy (OPAT). Compared with OPAT, oral therapy has lower costs and avoids catheter complications. However, few studies have specifically compared patient outcomes between those receiving oral therapy vs. OPAT for osteomyelitis with associated bacteremia caused by MRSA. Methods We performed a retrospective cohort study comparing early oral therapy (EOT), defined as transition to oral therapy at or prior to discharge vs. use of OPAT at discharge. We identified hospitalized children <19 years of age with MRSA osteomyelitis with bacteremia between 2007 and 2014 from three children's hospitals. The primary outcome was treatment failure within 6 months of discharge, defined as unplanned change in antibiotic after discharge, development of chronic osteomyelitis, need for an operative procedure after discharge, or recrudescence of bacteremia. The secondary outcome was treatment-related events, defined as documented adverse drug events in the medical record and/or central venous catheter complications. Between-group comparisons were made using Fisher exact test for binomial distributions and the Wilcoxon rank-sum test for continuous variables. Results We included 61 patients with MRSA osteomyelitis with bacteremia. Twenty-five patients (41%) received EOT and 36 (59%) received OPAT. Duration of bacteremia and hospital length of stay was similar between groups (Table 1). Clindamycin was the most commonly used antibiotic in both the EOT (24/25; 96%) and OPAT (22/36; 61%) groups. Clinical failure occurred in 1/25 (4%) children receiving EOT and in 5/36 (14%) in the OPAT group (95% CI of difference: −29 to 6%; P = 0.38, Table 1). Treatment-related adverse events occurred in 1/25 (4%) children receiving EOT compared with 9/36 (25%) receiving OPAT (95% CI of difference: −49 to –7%; P = 0.04, Table 1). Conclusion Children receiving EOT for MRSA osteomyelitis with bacteremia did not experience higher rates of clinical failure and had fewer treatment-related complications compared with OPAT. Oral step-down therapy can be considered for children with MRSA osteomyelitis with bacteremia. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Objective National guidelines recommend oral vancomycin over oral metronidazole as first-line treatment for nonsevere Clostridioides difficile infection (CDI) in adults. Guidelines recommend metronidazole for children with nonsevere CDI, emphasizing that comparative effectiveness studies comparing the relative efficacy of vancomycin and metronidazole are lacking in children. Method We conducted an observational study of hospitalized children with nonsevere CDI treated with metronidazole versus vancomycin using an inverse probability of treatment-weighted propensity-score analysis. All of the following criteria had to be present for children with positive CDI testing for study eligibility: (1) ≥3 new-onset unformed stools within a 24-hour period; (2) 2–17 years of age; (3) hospitalization for ≥48 hours for CDI; (4) no laxative use ≤48 hours; (5) no alternate etiology for diarrhea; (6) no previous episode of CDI ≤3 months; (7) no concurrent non-CDI–targeted antibiotic therapy, and (8) no severe or fulminant CDI. Results One hundred ninety-two patients met eligibility criteria; 141 (73.4%) received oral metronidazole and 51 (26.6%) children received oral vancomycin. Baseline characteristics were similar between the 2 groups in the weighted cohort. Of 141 patients, 101 (71.7%) children receiving metronidazole had clinical improvement by day 5, whereas 44 of 51 (86.3%) cases resolved with vancomycin (odds ratio, 0.40; 95% confidence interval, 0.17–0.97; P =.04). The odds of CDI recurrence within 12 weeks were similar between the groups. Conclusions Our study suggests that children with nonsevere CDI have earlier resolution of clinical symptoms when prescribed vancomycin compared with metronidazole. Large interventional studies are necessary to evaluate the reproducibility of our findings. [ABSTRACT FROM AUTHOR]